Abstract:
RATIONALE:Asthma commonly originates in early life in association with impaired lung function, which tracks to adulthood. OBJECTIVES:Within the context of a prospective birth cohort study, we investigated the association between single nucleotide polymorphisms (SNPs) in a disintegrin and metalloprotease 33 (ADAM33) gene and early-life lung function. METHODS:Children were genotyped for 17 SNPs in ADAM33. Lung function at age 3 (n = 285) and 5 years (n = 470) was assessed using plethysmographic measurement of specific airway resistance (sRaw). At age 5, we also measured FEV(1). SNPs were analyzed individually using logistic regression, followed by linkage disequilibrium mapping to identify the causal locus. MAIN RESULTS:Carriers of the rare allele of F+1 SNP had reduced lung function at age 3 years (p = 0.003). When the recessive model was considered, four SNPs (F+1, S1, ST+5, V4) showed association with sRaw at age 5 years (p < 0.04). Using linkage disequilibrium mapping, we found evidence of a significant causal location between BC+1 and F1 SNPs, at the 5' end of the gene. Four SNPs were associated with lower FEV(1) (F+1, M+1, T1, and T2; p < or = 0.04). The risk of transient early wheezing more than doubled among children homozygous for the A allele of F+1 (odds ratio, 2.39; 95% confidence intervals, 1.18-4.86; p = 0.02), but there was no association between any SNP and allergic sensitization or physician-diagnosed asthma. CONCLUSIONS:Polymorphisms in ADAM33 predict impaired early-life lung function. The functionally relevant polymorphism is likely to be at the 5' end of the gene.
journal_name
Am J Respir Crit Care Medauthors
Simpson A,Maniatis N,Jury F,Cakebread JA,Lowe LA,Holgate ST,Woodcock A,Ollier WE,Collins A,Custovic A,Holloway JW,John SLdoi
10.1164/rccm.200412-1708OCkeywords:
subject
Has Abstractpub_date
2005-07-01 00:00:00pages
55-60issue
1eissn
1073-449Xissn
1535-4970pii
200412-1708OCjournal_volume
172pub_type
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